Sickle Cell DiseasePhase 1/2NCT01499888
Ph I/II Study of Allogeneic SCT for Clinically Aggressive Sickle Cell Disease (SCD)
A Phase 1/2 study testing Allogeneic Non-Myeloablative Stem Cell Transplantation, Alemtuzumab and Sirolimus in people with Sickle Cell Disease, run by University of Illinois Chicago at 1 site in United States.
Trial summary
The investigators propose to determine the engraftment and transplant related morbidity and mortality after a non-myeloablative allogeneic hematopoietic stem cell transplant protocol using immune- suppressive agents and low-dose total body irradiation (TBI) without standard chemotherapy in patients with aggressive… Read more about this study
- Who is it for?
- Ages 16 to 60 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Allogeneic Non-Myeloablative Stem Cell Transplantation, Alemtuzumab and Sirolimus
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Nov 2011to Oct 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with sickle cell disease, subtype Hgb SS, SC, or SB disease who are on chronic transfusion therapy for a prior stroke or those patients who were intolerant of hydroxyurea therapy or were being treated with hydroxyurea therapy and were complicated by at least one of the following:
- Stroke or central nervous system event lasting longer than 24 hours
- Frequent vaso-occlusive pain episodes, defined as ≥ 3 per year severe enough to interfere with the patient's normal daily function or require medical attention in the clinic, emergency room, acute care center, or hospital
- Recurrent episodes of priapism, defined as ≥ 2 per year requiring emergency room visits
- Acute chest syndrome with recurrent hospitalizations, defined as ≥ 2 lifetime events
- Red-cell alloimmunization (≥ 2 antibodies) during longterm transfusion therapy
Show all 23Show fewer
- Bilateral proliferative retinopathy with major visual impairment in at least one eye
- Osteonecrosis of 2 or more joints
- Sickle cell nephropathy
- Stage I or II sickle lung disease
- Symptoms of pulmonary hypertension and mean pulmonary artery pressure > 25mmHg
- Age 16-60 years
- Karnofsky performance status of 70 or higher
- Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40%
- Adequate pulmonary function, defined as diffusion lung capacity of carbon monoxide ≥ 50%
- Estimated GFR ≥ 30mL/min as calculated by the modified MDRD equation
- ALT ≤ 3x upper limit of normal
- No evidence of chronic active hepatitis or cirrhosis
- HIV-negative
- Patient is not pregnant
- History of compliance with medications and medical care
- Patient is able and willing to sign informed consent
- Patient has an HLA-identical matched related donor
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Illinois at Chicago
Chicago, Illinois, 60612
About this study
Official title: Phase I/II Study of Allogeneic Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease (SCD)
The investigators propose to determine the engraftment and transplant related morbidity and mortality after a non-myeloablative allogeneic hematopoietic stem cell transplant protocol using immune- suppressive agents and low-dose total body irradiation (TBI) without standard chemotherapy in patients with aggressive sickle cell disease who are not candidates for or experienced complications from hydroxyurea therapy.
Fully HLA matched siblings will be used as donors for hematopoietic stem cells to reduce the risk of morbidity and mortality in this cohort of patients.
Read the detailed description
Sickle cell disease is an inherited defect caused by a mutation in the Beta globin gene affecting red blood cells. Symptoms begin at 6 months of life and often lead to debilitating vaso-occlusive pain crises, acute insults to vital organ systems,chronic organ injury, and decreased survival with median survival estimated at 42 years for men and 48 years for women. Several cohort studies have identified clinical and laboratory predictors for decreased survival which include acute complications, and chronic complications of sickle cell disease.
Hydroxyurea is the only FDA approved drug to help ameliorate symptoms associated with sickle cell disease. Two nonrandomized studies have suggested a reduction in mortality after 17 years of long term hydroxyurea treatment. However, the mortality rate is still high in the hydroxyurea cohort at 43.1% and only 38.1% of patients have a rise in fetal hemoglobin indicating that a significant percentage of patients still have aggressive disease despite hydroxyurea treatment. Hydroxyurea therapy also does not seem to prevent the development of pulmonary hypertension.
In the pediatric population, patients that have not clinically improved despite optimized hydroxyurea management are offered allogeneic stem cell transplantation. Until recently, the options were more limited in adults with sickle cell disease that had aggressive disease despite hydroxyurea therapy. Most rely on chronic red blood cell transfusions which carry significant risks of infection, iron overload, and alloimmunization. Up to 50% of patients with sickle cell disease who are on chronic transfusion therapy will develop allo-antibodies making further transfusions difficult with a high potential for hemolytic transfusion reactions.
Patients with sickle cell disease often have chronic underlying organ disease and so the effects of chemotherapy may be unpredictable and potentially more harmful, making low dose TBI more attractive as a safer modality for conditioning.
The investigators propose to determine the engraftment and transplant related morbidity and mortality after a non-myeloablative allogeneic hematopoietic stem cell transplant protocol using immune- suppressive agents and low-dose total body irradiation (TBI) without standard chemotherapy in patients with aggressive sickle cell disease who are not candidates for or experienced complications from hydroxyurea therapy.
Fully HLA matched siblings will be used as donors for hematopoietic stem cells to reduce the risk of morbidity and mortality in this cohort of patients.
An optional correlative trial will be conducted to compare ocular findings after stem cell transplantation with those findings before stem cell transplantation. Anterior and posterior ocular examination as well as objective tests will be performed on subjects.
- Conditions
- Sickle Cell Disease
- Being tested
- Allogeneic Non-Myeloablative Stem Cell Transplantation, Alemtuzumab, Sirolimus
- Keywords
- Sickle Cell Disease, Subtype Hgb SS, Subtype Hgb SC, Subtype Hgb SB, Chronic Transfusion Therapy, Prior Stroke, Allogeneic, Stem Cell Transplantation, Alemtuzumab, Sirolimus, Total Body Irradiation, Hydroxyurea Intolerant
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic Non-Myeloablative Stem Cell TransplantationProcedure or surgery
Alemtuzumab-based non-myeloablative allogeneic hematopoietic stem cell transplantation using immune-suppressive agents and low-dose total body irradiation (TBI) without standard chemotherapy.
Transplant regimen Day -7 to -3: Alemtuzumab (1mg/kg, total dose) divided over the 5 days, IVPB over 2 hours daily Day -3 until 100% chimerism obtained: Sirolimus dosed for target trough level of 10-15 ng/mL Day -2: Total body irradiation with 300cGy Day 0: Stem cell infusion
AlemtuzumabDrug
Also called Campath, MabCampath, Campath-1H
In this protocol, patients will be given alemtuzumab 1mg/kg divided equally over five days with the maximum dose of 20mg per day.
SirolimusDrug
Also called Rapamune, Rapamycin
On day -1, patients will receive a loading dose of 12 mg followed by 4 mg per day. Subsequent dosing will be based on clinical toxicity, GVHD concurrent medications, medical conditions, prior drug levels, drug-drug interactions, and blood levels with target of 3 to 12 ng/mL.
| Study group | Role | What they receive |
|---|---|---|
| Allogeneic Non-Myeloablative Stem Cell Transplantation | Experimental | The transplant regimen will consist of alemtuzumab 1mg/kg divided over five days, 300 cGy TBI, followed by sirolimus dosed for a target serum trough level of 10- 15 ng/mL. Receives: Procedure: Allogeneic Non-Myeloablative Stem Cell Transplantation; Drug: Alemtuzumab; Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the engraftment after non-myeloablative HSC transplant
Measured: Up to 30 days post-transplant.
Secondary outcomes (4)
To assess the frequency of acute and chronic complications of sickle cell disease
To assess for the frequency of acute and chronic complications of sickle cell disease after allogeneic hematopoietic stem cell transplantation using a protocol of immunosuppressive agents and low-dose TBI without standard chemotherapy. The acute complications include vaso-occlusive pain episodes, acute chest syndrome, stroke, and priapism. The chronic complications include nephropathy, retinopathy, osteonecrosis, pulmonary artery pressures, and chronic lung disease.
Measured: Up to 100 days post-transplant.
To evaluate the immune reconstitution after transplant.
Measured: Up to 12 months after transplant.
To determine the transplant related morbidity and mortality.
Transplant related mortality will be evaluated at day 100 and day 365. If mortality is greater than 25% at day 100 or 35% at day 365, then the trial will be closed.
Measured: Up to 365 days post-transplant.
To determine the long-term engraftment after non-myeloablative HSC transplant
Measured: Up to 10 years post-transplant.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2011 (estimated)
- Study start11 Nov 2011
- Primary completion23 Sep 2028 (estimated)
- Study completionOct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by University of Illinois ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Illinois Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Damiano Rondelli, MD, University of Illinois Chicago
- Investigators
- Damiano Rondelli, MD, Principal investigator, University of Illinois Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01499888
- Sponsor's protocol ID
- 2011-0096
- Status last verified
- Jul 2026
- First submitted
- 23 Nov 2011
- Last updated
- 8 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Allogeneic Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease (SCD)
- ClinicalTrials.gov ID
- NCT01499888
- Acronym / sponsor ID
- 2011-0096
- Conditions
- Sickle Cell Disease
- Keywords
- Sickle Cell Disease, Subtype Hgb SS, Subtype Hgb SC, Subtype Hgb SB, Chronic Transfusion Therapy, Prior Stroke, Allogeneic, Stem Cell Transplantation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 45 participants (actual)
- Lead sponsor
- University of Illinois ChicagoUniversity, hospital or other
- Study start
- 11 Nov 2011 (actual)
- Primary completion
- 23 Sep 2028 (estimated)
- Study completion
- Oct 2029 (estimated)
- First posted
- 26 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators propose to determine the engraftment and transplant related morbidity and mortality after a non-myeloablative allogeneic hematopoietic stem cell transplant protocol using immune- suppressive agents and low-dose total body irradiation (TBI) without standard chemotherapy in patients with aggressive sickle cell disease who are not candidates for or experienced complications from hydroxyurea therapy.
Fully HLA matched siblings will be used as donors for hematopoietic stem cells to reduce the risk of morbidity and mortality in this cohort of patients.
Detailed description
Sickle cell disease is an inherited defect caused by a mutation in the Beta globin gene affecting red blood cells. Symptoms begin at 6 months of life and often lead to debilitating vaso-occlusive pain crises, acute insults to vital organ systems,chronic organ injury, and decreased survival with median survival estimated at 42 years for men and 48 years for women. Several cohort studies have identified clinical and laboratory predictors for decreased survival which include acute complications, and chronic complications of sickle cell disease.
Hydroxyurea is the only FDA approved drug to help ameliorate symptoms associated with sickle cell disease. Two nonrandomized studies have suggested a reduction in mortality after 17 years of long term hydroxyurea treatment. However, the mortality rate is still high in the hydroxyurea cohort at 43.1% and only 38.1% of patients have a rise in fetal hemoglobin indicating that a significant percentage of patients still have aggressive disease despite hydroxyurea treatment. Hydroxyurea therapy also does not seem to prevent the development of pulmonary hypertension.
In the pediatric population, patients that have not clinically improved despite optimized hydroxyurea management are offered allogeneic stem cell transplantation. Until recently, the options were more limited in adults with sickle cell disease that had aggressive disease despite hydroxyurea therapy. Most rely on chronic red blood cell transfusions which carry significant risks of infection, iron overload, and alloimmunization. Up to 50% of patients with sickle cell disease who are on chronic transfusion therapy will develop allo-antibodies making further transfusions difficult with a high potential for hemolytic transfusion reactions.
Patients with sickle cell disease often have chronic underlying organ disease and so the effects of chemotherapy may be unpredictable and potentially more harmful, making low dose TBI more attractive as a safer modality for conditioning.
The investigators propose to determine the engraftment and transplant related morbidity and mortality after a non-myeloablative allogeneic hematopoietic stem cell transplant protocol using immune- suppressive agents and low-dose total body irradiation (TBI) without standard chemotherapy in patients with aggressive sickle cell disease who are not candidates for or experienced complications from hydroxyurea therapy.
Fully HLA matched siblings will be used as donors for hematopoietic stem cells to reduce the risk of morbidity and mortality in this cohort of patients.
An optional correlative trial will be conducted to compare ocular findings after stem cell transplantation with those findings before stem cell transplantation. Anterior and posterior ocular examination as well as objective tests will be performed on subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Allogeneic Non-Myeloablative Stem Cell Transplantation | Experimental | Procedure: Allogeneic Non-Myeloablative Stem Cell Transplantation, Drug: Alemtuzumab, Drug: SirolimusThe transplant regimen will consist of alemtuzumab 1mg/kg divided over five days, 300 cGy TBI, followed by sirolimus dosed for a target serum trough level of 10- 15 ng/mL. |
Who may qualify
- Ages
- 16 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (23 listed)
- Patients with sickle cell disease, subtype Hgb SS, SC, or SB disease who are on chronic transfusion therapy for a prior stroke or those patients who were intolerant of hydroxyurea therapy or were being treated with hydroxyurea therapy and were complicated by at least one of the following:
- Age 16-60 years
- Karnofsky performance status of 70 or higher
- Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40%
- Adequate pulmonary function, defined as diffusion lung capacity of carbon monoxide ≥ 50%
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Allogeneic Non-Myeloablative Stem Cell TransplantationAlemtuzumab-based non-myeloablative allogeneic hematopoietic stem cell transplantation using immune-suppressive agents and low-dose total body irradiation (TBI) without standard chemotherapy. Transplant regimen Day -7 to -3: Alemtuzumab (1mg/kg, total dose) divided over the 5 days, IVPB over 2 hours daily Day -3 until 100% chimerism obtained: Sirolimus dosed for target trough level of 10-15 ng/mL Day -2: Total body irradiation with 300cGy Day 0: Stem cell infusion | Procedure or surgery | Allogeneic Non-Myeloablative Stem Cell Transplantation |
| AlemtuzumabAlso: Campath, MabCampath, Campath-1HIn this protocol, patients will be given alemtuzumab 1mg/kg divided equally over five days with the maximum dose of 20mg per day. | Drug | Allogeneic Non-Myeloablative Stem Cell Transplantation |
| SirolimusAlso: Rapamune, RapamycinOn day -1, patients will receive a loading dose of 12 mg followed by 4 mg per day. Subsequent dosing will be based on clinical toxicity, GVHD concurrent medications, medical conditions, prior drug levels, drug-drug interactions, and blood levels with target of 3 to 12 ng/mL. | Drug | Allogeneic Non-Myeloablative Stem Cell Transplantation |
Primary outcome
To determine the engraftment after non-myeloablative HSC transplant
Time frame: Up to 30 days post-transplant.
4 secondary outcomes
To assess the frequency of acute and chronic complications of sickle cell disease
Time frame: Up to 100 days post-transplant.
To evaluate the immune reconstitution after transplant.
Time frame: Up to 12 months after transplant.
To determine the transplant related morbidity and mortality.
Time frame: Up to 365 days post-transplant.
To determine the long-term engraftment after non-myeloablative HSC transplant
Time frame: Up to 10 years post-transplant.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Damiano Rondelli, MD principal investigator
University of Illinois Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Allogeneic Non-Myeloablative Stem Cell Transplantation, Alemtuzumab and Sirolimus in people with Sickle Cell Disease, run by University of Illinois Chicago at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the engraftment after non-myeloablative HSC transplant (time frame: Up to 30 days post-transplant.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.